Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000056661 | SCV004294173 | pathogenic | not provided | 2023-08-08 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 331 of the KRT5 protein (p.Arg331His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant epidermolysis bullosa (PMID: 16786515, 20060687, 21375516). ClinVar contains an entry for this variant (Variation ID: 66299). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on KRT5 protein function. This variant disrupts the p.Arg331 amino acid residue in KRT5. Other variant(s) that disrupt this residue have been observed in individuals with KRT5-related conditions (PMID: 16786515, 18704110, 20199538), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |
| Prevention |
RCV003894912 | SCV004709600 | likely pathogenic | KRT5-related condition | 2023-11-14 | criteria provided, single submitter | clinical testing | The KRT5 c.992G>A variant is predicted to result in the amino acid substitution p.Arg331His. This variant has been reported in individuals with epidermolysis bullosa simplex (Müller et al. 2006. PubMed ID: 16786515; Bolling et al. 2011. PubMed ID: 21375516). An alternative nucleotide change affecting the same amino acid (c.991C>T, p.Arg331Cys) has also been reported in individuals with epidermolysis bullosa simplex (Rugg et al. 1993. PubMed ID: 7506097). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as likely pathogenic. |
| Epithelial Biology; Institute of Medical Biology, |
RCV000056661 | SCV000087774 | not provided | not provided | no assertion provided | not provided |